ABCP Regimen Shows OS Benefit in Secondline NSCLC With EGFR Sensitizing Mutations

The combination of atezolizumab (Tecentriq) plus bevacizumab (Avastin) plus carboplatin, and paclitaxel (ABCP) showed stronger overall survival benefit compared with bevacizumab plus carboplatin and paclitaxel (BCP) for patients with sensitizing EGFR mutations in their non-small cell lung cancer (NSCLC), who previously failed TKIs, and with liver metastases. However, further investigation is required to see ABCP’s effect on delaying the development of new brain lesions, according to research published in the Journal of Thoracic Oncology.¹

Data were from a subgroup analysis of the phase 3 Impower150 study (NCT02366143) that looked at 1202 patients with chemotherapy-naive, metastatic, nonsquamous NSCLC randomized to either ABCP, BCP, or atezolizumab plus carboplatin and paclitaxel.

After data cutoff and a median follow up of 39.3 months, OS improvements were sustained in patients with EGFR mutations on ABCP (n = 34) compared to those on BCP (n = 44) at 29.4 months versus 18.1 months, respectively (HR 0.60; 95% CI, 0.31–1.14). Furthermore, the median OS was similar in patients on BCP compared to ACP at 19 months and 18.1 months, respectively (HR 1.00; 95% CI, 22.1-61.6). Stronger OS results with ABCP extended to the 3-year OS rate in patients with EGFR mutations at 41.9% (95% CI, 22.1-61.6%) compared to 25.6% (95% CI, 10.4%-40.8%) in the ACP arm, and 24.6% (95% CI, 9.5%-39.7%) in the BCP arm.

In patients who received previous TKI therapies but had an EGFR mutation in their disease median OS was also longer in the ABCP arm at 27.8 months compared to 18.1 months in the BCP arm (HR, 0.74; 95% CI, 0.38-1.46). No OS benefit was seen in patients in the ACP arm with EGFR mutations who failed TKI therapy at 14.9 months. The 3-year OS rate in this subgroup was also stronger in the ABCP arm at 35.3% compared to 15.4% in the ACP arm, and 24.5% in the BCP arm.

Patients in the intention to treat population who developed liver metastases also had a higher median OS on ABCP at 13.2 months compared to 9.1 months in the BCP arm (HR, 0.68; 95% CI, 0.45-1.02) while no OS benefit was observed in the ACP arm at 7.7 months.

“It may be speculated that increased sensitivity to bevacizumab through promotion of VEGF expression in EGFR-mutant tumors or reversal of immune suppression by bevacizumab against a background of reduced CD8-positive T-cell infiltration in patients with EGFR mutations or liver metastases may further enhance T-cell–mediated killing by atezolizumab,” researchers explained in the study discussion. “Moreover, low PD-L1 prevalence rates across treatment arms suggest that the observed clinical benefit of ABCP was not solely driven by PD-L1–high expression and is consistent with previous evidence suggesting PD-L1 expression does not predict benefit in EGFR-mutant NSCLC.”

100 patients developed new brain metastases at the time of data cutoff, with median time to development not being reached in either arm of the trial. The range in the ABCP arm was 0-45.9 months (HR, 0.68; 95% CI, 0.39-1.19), compared to 0-46.9 months (HR 1.55; 95% CI, 0.95-2.55) in the ACP arm, and 0-42.3 months in the BCP arm. Researchers believe that more study would be needed to assess ABCP’s effectiveness in delaying the development of brain metastases, moreover, they caution that these overall results need to be explored further as the subgroups had small differences between the number of patients in them.

In relation to the overall Impower150 study the researchers found no new safety signals in the subgroups and that overall adverse event (AE) profiles were consistent with the main study. In those patients with EGFR mutations grade 3/4 AEs were reported in 66.7% of patients in the ABCP arm, compared to 56.8% in the ACP arm, and 55.8% in the BCP arm. Only 1 patient in the BCP arm experienced a grade 5 AE while no patients in the atezolizumab arms experienced a severe AE.

AEs that led to treatment withdrawal were experienced by 42.4% of patients in the ABCP arm, 13.6% in the ACP arm, and 16.3% in the BCP arm. Most patients with a liver metastasis also experienced an AE, regardless of the study arm they were, with the majority of those patients being the ones in the ABCP arm at 100%.“ABCP is advocated as a standard-of-care regimen for the first-line treatment of metastatic nonsquamous NSCLC,” the researchers concluded. “This updated analysis reveals possible survival gains with ABCP in key patient subgroups, highlighting this regimen as a potential new treatment option for difficult-to-treat patients with poor prognostic outcomes, such as those with liver metastases or sensitizing EGFR mutations for whom TKIs have failed.”

_Reference

_{Nogami N, Barlesi F, Socinski MA, et al. IMpower150 Final Exploratory Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in Key NSCLC Patient Subgroups With EGFR Mutations or Metastases in the Liver or Brain. J Thorac Oncol. 2022;17(2):309-323. doi: 10.1016/j.jtho.2021.09.014}